A Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC)

• Sponsor: Bayer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00558636
• Collaborator: (none)
• Enrollment: 91
• Locations: 22
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study conducted in Asia-Pacific was to evaluate the efficacy and safety of Sorafenib in combination with paclitaxel and carboplatin versus placebo in combination with paclitaxel and carboplatin for chemonaive patients with unresectable stage IIIB (with effusion) or stage IV NSCLC. However, as indicated below, the study was terminated prematurely when the results from Study 11961 (NCT00300885), an earlier Phase 3 study of similar design in subjects with advanced NSCLC, showed an overall lack of efficacy and increased mortality in subjects with squamous subtype. The data available is presented as descriptive analyses, due to the limitations of implementing the statistical analysis plan.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Sorafenib + Paclitaxel + Carboplatin; Drug: Placebo + Paclitaxel + Carboplatin	Phase 3

Detailed Description

The study was terminated early when the results from Study 11961 (NCT00300885), an earlier Phase 3 study evaluating the effects of Sorafenib in combination with paclitaxel and carboplatin in subjects with advanced NSCLC, showed an overall lack of efficacy of Sorafenib in combination with paclitaxel and carboplatin in NSCLC and increased mortality in subjects with squamous subtype.

Study Design

• Study Type: Interventional
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC)
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sorafenib + Paclitaxel + Carboplatin Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.	Drug: Sorafenib + Paclitaxel + Carboplatin; Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.
Placebo Comparator: Placebo + Paclitaxel + Carboplatin Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days	Drug: Placebo + Paclitaxel + Carboplatin; Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [Up to 5 months after randomization of the first patient]

   Progression free survival (PFS) is the time (days) from date of randomization to date of first observed disease progression (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before progression was documented. Since the study was terminated early and 89% of subjects' data were censored, only the number of PFS events (Failed [progressed or died before progression]) is reported, not the usual measure "number of days".

Secondary Outcome Measures

1. Overall Survival (OS) [Up to 5 months after randomization of the first patient]

   Overall survival is the number of days from the date of randomization to the date of death due to any cause. Subjects alive at the time of analysis were censored at their last date of follow-up. Since the study was terminated early and 89% of subjects' data were censored, only the number of subjects who Failed (died) or were Censored is reported, not the usual measure "number of days".

2. Best Tumor Response (Number of Responses Per Category) According to Response Evaluation Criteria in Solid Tumors (RECIST) [Best tumor response assessed every 6 weeks by investigator during treatment up to 5 months after randomization of the first patient.]

   Complete response (CR): Disappearance of all target lesions (TL). Partial response (PR): At least 30% decrease in sum of the largest diameter (LD) of TLs, taking baseline sum as reference. Stable disease (SD): No change in tumor size. Progressive disease (PD): At least a 20% increase in the sum of the LD of TLs, taking as reference the smallest sum LD recorded since treatment started, or the appearance of 1 or more new lesions.

3. Duration of Response [Time from first documented objective response (complete response or partial response) to disease progression or death, or to last tumor assessment if censored, up to 5 months after randomization of the first patient.]

   Duration of response (PR or better) was defined as the time from the first documented objective PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). Since only 4 subjects had a response, the duration of response was not calculated.

4. Change From Baseline of Lung Cancer Symptoms (LCS) Score Assessed at Each Treatment Cycle (21 Days Per Cycle) Starting With Cycle 2 [Change from baseline of LCS score assessed at each treatment cycle starting with Cycle 2 (Cycles 2, 3, 4, 5, 6, 7; 21 days per cycle) up to 5 months after randomization of the first patient.]

   The LCS is a validated instrument for determining treatment impact on lung symptoms. The LCS consists of 7 questions with 5 responses ranging from "not at all" to "very much". The LCS total score ranges from 0 to 28. Lower scores reflect greater lung cancer symptoms.

5. Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 3 and Cycle 5 [Change from baseline of HRQoL score assessed (at treatment Cycle 3 and Cycles 5 [21 days per cycle]) up to 5 months after randomization of the first patient.]

   HRQoL was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, a validated instrument for determining lung cancer HRQoL. The 36-item questionnaire includes 4 domains: Physical, functional, emotional, and social/family well-being, and a lung cancer-specific subscale. The FACT-L total score ranges from 1 to 136. Lower scores demonstrate impaired HRQoL.

6. Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 7 [Change from baseline of HRQoL score assessed (at treatment Cycle 7 [21 days per cycle]) up to 5 months after randomization of the first patient.]

   HRQoL was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, a validated instrument for determining lung cancer HRQoL. The 36-item questionnaire includes 4 domains: Physical, functional, emotional, and social/family well-being, and a lung cancer-specific subscale. The FACT-L total score ranges from 1 to 136. Lower scores demonstrate impaired HRQoL.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Stage IIIB (with cytologically confirmed malignant pleural or pericardial effusion) or Stage IV histological or cytological confirmation of NSCLC (thoracentesis or pericardiocentesis is not necessary if a biopsy of the original tumor is available to confirm diagnosis of NSCLC)

• Patients must have measurable disease according to response evaluation criteria in solid tumors (RECIST) criteria

• Prior local radiotherapy is allowed if it is completed at least 3 weeks prior to the first dose of study drug, but the lesion which undergo RECIST assessment should not be in the field of the prior radiation

• Prior surgery is allowed if it is performed at least 4 weeks prior to the first dose of study drug

• 18 years and above

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

• Life expectancy of at least 12 weeks

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose:

• Hemoglobin 9.0 g/dl

• Absolute neutrophil count (ANC) 1,500/mm3

• Platelet count 100,000/mm3

• Total bilirubin < 1.5 times the upper limit of normal

• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement)

• international normalized ratio (INR) < 1.5 and activated or adjusted partial thromboplastin time (APTT) within normal limits (1.2 times the lower limit of normal (LLN) to 1.2 times the upper limit of normal (ULN))

• Creatinine </= 1.5 times the upper limit of normal

• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures

Exclusion Criteria:

• Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy, adjuvant, or neo-adjuvant therapy for any current or prior diagnosis of NSCLC

• Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina (began within the last 3 months) or myocardial infarction within the past 6 months

• Known brain metastasis. Patients with neurological symptoms should undergo at Computed Tomography (CT) scan/Magnetic Resonance Imaging (MRI) of the brain to exclude brain metastasis

• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

• Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management

• Known human immunodeficiency virus (HIV) infection

• Active clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2

• Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months

• Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug

• Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug

• Serious, non-healing wound, ulcer, or bone fracture

• Evidence or history of bleeding diathesis or coagulopathy

• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug

• Therapeutic anticoagulation with vitamin K antagonists such as warfarin, or with heparins or heparinoids. Low dose warfarin (1 mg daily, oral) is permitted if the INR remains < 1.5. Low-dose aspirin is permitted

• Known or suspected allergy to sorafenib or any agent given in the course of this trial

• Cancer other than NSCLC within 5 years prior to start of study treatment, EXCEPT cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumors

• Concurrent cancer that is distinct in primary site or histology from NSCLC

• Substance abuse, medical, psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results

• Any condition that impairs patients ability to swallow whole pills

• Any malabsorption condition

• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment

• Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation, including the 30 days period after last study drug dosing. The investigator should advise the patient how to achieve an adequate contraception

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Guangzhou	Guangdong	China	510060
2		Guangzhou	Guangdong	China	510515
3		Shatin	Hong Kong	China
4		Nanjing	Jiangsu	China	210003
5		Hangzhou	Zhejiang	China	(310022),
6		Hangzhou	Zhejiang	China	310016
7		Beijing		China	100021
8		Beijing		China	100142
9		Beijing		China	100730
10		Chongqing		China	400038
11		Shanghai		China	200032
12		Shanghai		China	200433
13		Mumbai	Maharashtra	India	400012
14		New- Delhi		India	110008
15		Gyeonggi-do		Korea, Republic of	410-769
16		Seoul		Korea, Republic of	136-705
17		Singapore		Singapore	119228
18		Singapore		Singapore	169610
19		Changhua		Taiwan	500
20		Taipei		Taiwan	100
21		Bangkok		Thailand	10330
22		Bangkok		Thailand

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00558636
• Other Study ID Numbers: 12621
• First Posted: Nov 15, 2007
• Last Update Posted: Dec 27, 2013
• Last Verified: Dec 1, 2013

• Keywords provided by Bayer: NSCLC
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Paclitaxel; Albumin-Bound Paclitaxel; Carboplatin; Sorafenib

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from 23 Sep 2007 to 12 May 2008 (first subject's first visit to last subject's last visit) at 15 centers in 4 countries: China (9), Singapore (2), Thailand (2), and Taiwan (2). The study was terminated prematurely after about 5 months of recruitment and before the planned 230 progression free survival (PFS) events occurred.
Pre-assignment Detail	At the time of study termination, 91 (out of 108 screened subjects) of the planned 294 subjects had been screened and randomized. All 91 randomized subjects received at least 1 dose of study drug and were included in both the intent-to-treat (ITT) and safety analysis populations.

Arm/Group Title	Sorafenib + Paclitaxel + Carboplatin	Placebo + Paclitaxel + Carboplatin
Arm/Group Description	Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.	Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days
Period Title: Treatment
STARTED	47	44
Start of Maintenance Monotherapy	2	2
COMPLETED	0	0
NOT COMPLETED	47	44
Period Title: Treatment
STARTED	12	7
COMPLETED	0	0
NOT COMPLETED	12	7

Baseline Characteristics

Arm/Group Title	Sorafenib + Paclitaxel + Carboplatin	Placebo + Paclitaxel + Carboplatin	Total
Arm/Group Description	Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.	Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days	Total of all reporting groups
Overall Participants	47	44	91
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	38 80.9%	32 72.7%	70 76.9%
>=65 years	9 19.1%	12 27.3%	21 23.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.2 (9.3)	55.4 (12.6)	55.8 (11.0)
Sex: Female, Male (Count of Participants)
Female	20 42.6%	14 31.8%	34 37.4%
Male	27 57.4%	30 68.2%	57 62.6%
Eastern Cooperative Oncology Group (ECOG) performance status (Number) [Number]
Grade 0: Fully active	8 17%	5 11.4%	13 14.3%
Grade 1: Restricted strenuous activity, ambulatory	39 83%	39 88.6%	78 85.7%
Geographic region (Number) [Number]
China	35 74.5%	36 81.8%	71 78%
Non-China	12 25.5%	8 18.2%	20 22%
Histology (Number) [Number]
Squamous cell (epidermoid) carcinoma	13 27.7%	14 31.8%	27 29.7%
Other	33 70.2%	30 68.2%	63 69.2%
Missing histology	1 2.1%	0 0%	1 1.1%
Stage at study entry (Number) [Number]
Missing	3 6.4%	1 2.3%	4 4.4%
Stage IIIB	7 14.9%	3 6.8%	10 11%
Stage IV	37 78.7%	40 90.9%	77 84.6%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Description	Progression free survival (PFS) is the time (days) from date of randomization to date of first observed disease progression (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before progression was documented. Since the study was terminated early and 89% of subjects' data were censored, only the number of PFS events (Failed [progressed or died before progression]) is reported, not the usual measure "number of days".
Time Frame	Up to 5 months after randomization of the first patient

Outcome Measure Data

Analysis Population Description

It was intended to include all randomized subjects (the intent to treat (ITT) population) in the analysis. Since 89% of subjects were censored, PFS could not be calculated. The number of subjects who Failed (progressed or died before progression) or were Censored are reported.

Arm/Group Title	Sorafenib + Paclitaxel + Carboplatin	Placebo + Paclitaxel + Carboplatin
Arm/Group Description	Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.	Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days
Measure Participants	47	44
Failed (progressed or died before progression)	5 10.6%	5 11.4%
Censored	42 89.4%	39 88.6%

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is the number of days from the date of randomization to the date of death due to any cause. Subjects alive at the time of analysis were censored at their last date of follow-up. Since the study was terminated early and 89% of subjects' data were censored, only the number of subjects who Failed (died) or were Censored is reported, not the usual measure "number of days".
Time Frame	Up to 5 months after randomization of the first patient

Outcome Measure Data

Analysis Population Description

All randomized subjects (the intent to treat (ITT) population) were included in the analysis. Since 89% of subjects were censored, OS could not be calculated. The number of subjects who Failed (died) or were Censored are reported.

Arm/Group Title	Sorafenib + Paclitaxel + Carboplatin	Placebo + Paclitaxel + Carboplatin
Arm/Group Description	Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.	Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days
Measure Participants	47	44
Failed (died)	4 8.5%	1 2.3%
Censored	43 91.5%	43 97.7%

3. Secondary Outcome

Title	Best Tumor Response (Number of Responses Per Category) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Description	Complete response (CR): Disappearance of all target lesions (TL). Partial response (PR): At least 30% decrease in sum of the largest diameter (LD) of TLs, taking baseline sum as reference. Stable disease (SD): No change in tumor size. Progressive disease (PD): At least a 20% increase in the sum of the LD of TLs, taking as reference the smallest sum LD recorded since treatment started, or the appearance of 1 or more new lesions.
Time Frame	Best tumor response assessed every 6 weeks by investigator during treatment up to 5 months after randomization of the first patient.

Outcome Measure Data

Analysis Population Description

All randomized subjects (the intent to treat (ITT) population) were included in the analysis.

Arm/Group Title	Sorafenib + Paclitaxel + Carboplatin	Placebo + Paclitaxel + Carboplatin
Arm/Group Description	Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.	Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days
Measure Participants	47	44
Complete repsonse (CR)	0 0%	0 0%
Partial response (PR)	4 8.5%	0 0%
Stable disease (SD)	18 38.3%	28 63.6%
Progressive disease (PD)	1 2.1%	1 2.3%
not evaluated	24 51.1%	15 34.1%

4. Secondary Outcome

Title	Duration of Response
Description	Duration of response (PR or better) was defined as the time from the first documented objective PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). Since only 4 subjects had a response, the duration of response was not calculated.
Time Frame	Time from first documented objective response (complete response or partial response) to disease progression or death, or to last tumor assessment if censored, up to 5 months after randomization of the first patient.

Outcome Measure Data

Analysis Population Description

All subjects that showed a response. Since only 4 subjects had a response, the data were not analyzed.

Arm/Group Title	Sorafenib + Paclitaxel + Carboplatin	Placebo + Paclitaxel + Carboplatin
Arm/Group Description	Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.	Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days
Measure Participants	4	0
The first subject who showed a response	91
The second subject who showed a response	45
The third subject who showed a response	46
The fourth subject who showed a response	53

5. Secondary Outcome

Title	Change From Baseline of Lung Cancer Symptoms (LCS) Score Assessed at Each Treatment Cycle (21 Days Per Cycle) Starting With Cycle 2
Description	The LCS is a validated instrument for determining treatment impact on lung symptoms. The LCS consists of 7 questions with 5 responses ranging from "not at all" to "very much". The LCS total score ranges from 0 to 28. Lower scores reflect greater lung cancer symptoms.
Time Frame	Change from baseline of LCS score assessed at each treatment cycle starting with Cycle 2 (Cycles 2, 3, 4, 5, 6, 7; 21 days per cycle) up to 5 months after randomization of the first patient.

Outcome Measure Data

Analysis Population Description

Of the 91 randomized subjects in the ITT population, 90 completed the LCS at baseline. Since more than half of the subjects received only 1 or 2 cycles before the trial was stopped, the response rate (number of evaluable subjects completing the questionnaire) decreased from cycle to cycle and makes the results hard to interpret.

Arm/Group Title	Sorafenib + Paclitaxel + Carboplatin	Placebo + Paclitaxel + Carboplatin
Arm/Group Description	Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.	Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days
Measure Participants	47	43
Cycle 2 (N = 31 sorafenib/33 placebo)	2.8 (10.0)	1.1 (5.6)
Cycle 3 (N = 16 sorafenib/23 placebo)	0.4 (3.6)	0.2 (13.2)
Cycle 4 (N = 12 sorafenib/14 placebo)	-0.1 (3.0)	2.2 (4.2)
Cycle 5 (N = 7 sorafenib/5 placebo)	2.4 (2.7)	3.6 (4.5)
Cycle 6 (N = 4 sorafenib/3 placebo)	-0.8 (2.9)	4.3 (8.6)
Cycle 7 (N = 2 sorafenib/1 placebo)	3.0 (2.8)	0 (0)

6. Secondary Outcome

Title	Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 3 and Cycle 5
Description	HRQoL was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, a validated instrument for determining lung cancer HRQoL. The 36-item questionnaire includes 4 domains: Physical, functional, emotional, and social/family well-being, and a lung cancer-specific subscale. The FACT-L total score ranges from 1 to 136. Lower scores demonstrate impaired HRQoL.
Time Frame	Change from baseline of HRQoL score assessed (at treatment Cycle 3 and Cycles 5 [21 days per cycle]) up to 5 months after randomization of the first patient.

Outcome Measure Data

Analysis Population Description

Of the 91 randomized subjects in the ITT population, 88 completed the FACT-L at baseline. Since more than half of the subjects received only 1 or 2 cycles before the trial was stopped, the number of subjects who completed the questionnaire after the first cycles was very low, making the results difficult to interpret.

Arm/Group Title	Sorafenib + Paclitaxel + Carboplatin	Placebo + Paclitaxel + Carboplatin
Arm/Group Description	Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.	Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days
Measure Participants	46	42
Cycle 3 (N = 16 sorafenib/21 placebo)	-5.1 (10.6)	4.6 (19.5)
Cycle 5 (N = 7 sorafenib/5 placebo)	0 (9.9)	11.2 (27.8)

7. Secondary Outcome

Title	Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 7
Description	HRQoL was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, a validated instrument for determining lung cancer HRQoL. The 36-item questionnaire includes 4 domains: Physical, functional, emotional, and social/family well-being, and a lung cancer-specific subscale. The FACT-L total score ranges from 1 to 136. Lower scores demonstrate impaired HRQoL.
Time Frame	Change from baseline of HRQoL score assessed (at treatment Cycle 7 [21 days per cycle]) up to 5 months after randomization of the first patient.

Outcome Measure Data

Analysis Population Description

Of the 91 randomized subjects in the ITT population, 88 completed the FACT-L at baseline. Since more than half of the subjects received only 1 or 2 cycles before the trial was stopped, the number of subjects who completed the questionnaire after the first cycles was very low, making the results difficult to interpret.

Arm/Group Title	Sorafenib + Paclitaxel + Carboplatin	Placebo + Paclitaxel + Carboplatin
Arm/Group Description	Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.	Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days
Measure Participants	2	1
Mean (Standard Deviation) [Units on a scale]	13.5 (6.4)	11.3

Adverse Events

Adverse Event Reporting Description	The following acronyms and abbreviations were used in the Results section: Absolute Neutrophil Count (ANC); Not Otherwise Specified (NOS); Alanine aminotransferase (ALT); Gastrointestinal (GI)
Arm/Group Title	Sorafenib + Paclitaxel + Carboplatin		Placebo + Paclitaxel + Carboplatin
Arm/Group Description	Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.		Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days
All Cause Mortality
	Sorafenib + Paclitaxel + Carboplatin		Placebo + Paclitaxel + Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sorafenib + Paclitaxel + Carboplatin		Placebo + Paclitaxel + Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/47 (23.4%)		3/44 (6.8%)
Blood and lymphatic system disorders
Neutrophiles	1/47 (2.1%)		0/44 (0%)
General disorders
Pain, abdomen NOS	1/47 (2.1%)		0/44 (0%)
Immune system disorders
Allergic reaction	0/47 (0%)		1/44 (2.3%)
Infections and infestations
Febrile Neutropenia	3/47 (6.4%)		0/44 (0%)
Infection (documented clinically), Lung (Pneumonia)	1/47 (2.1%)		0/44 (0%)
Infection with normal ANC, blood	1/47 (2.1%)		0/44 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/47 (2.1%)		1/44 (2.3%)
Hypoxia	1/47 (2.1%)		0/44 (0%)
Pleural effusion	1/47 (2.1%)		0/44 (0%)
Pneumonitis	1/47 (2.1%)		0/44 (0%)
Skin and subcutaneous tissue disorders
Erythema multiforme	2/47 (4.3%)		0/44 (0%)
Rash/Desquamation	2/47 (4.3%)		0/44 (0%)
Vascular disorders
Thrombosis/Embolism (vascular access)	0/47 (0%)		1/44 (2.3%)
Other (Not Including Serious) Adverse Events
	Sorafenib + Paclitaxel + Carboplatin		Placebo + Paclitaxel + Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/47 (95.7%)		39/44 (88.6%)
Blood and lymphatic system disorders
Hemoglobin	12/47 (25.5%)		5/44 (11.4%)
Leukocytes	14/47 (29.8%)		10/44 (22.7%)
Neutrophils	31/47 (66%)		25/44 (56.8%)
Platelets	18/47 (38.3%)		7/44 (15.9%)
Lymphopenia	4/47 (8.5%)		4/44 (9.1%)
Cardiac disorders
Supraventricular arrhythmia, sinus tachycardia	0/47 (0%)		3/44 (6.8%)
Hypertension	8/47 (17%)		1/44 (2.3%)
Gastrointestinal disorders
Anorexia	6/47 (12.8%)		10/44 (22.7%)
Diarrhea	14/47 (29.8%)		7/44 (15.9%)
Constipation	8/47 (17%)		8/44 (18.2%)
GI-other	3/47 (6.4%)		0/44 (0%)
Nausea	7/47 (14.9%)		5/44 (11.4%)
Vomiting	7/47 (14.9%)		4/44 (9.1%)
General disorders
Fatigue	11/47 (23.4%)		12/44 (27.3%)
Fever	13/47 (27.7%)		3/44 (6.8%)
Insomnia	3/47 (6.4%)		1/44 (2.3%)
Pain, bone	3/47 (6.4%)		2/44 (4.5%)
Pain, extremity-limb	2/47 (4.3%)		6/44 (13.6%)
Pain, joint	2/47 (4.3%)		7/44 (15.9%)
Pain, muscle	7/47 (14.9%)		8/44 (18.2%)
Immune system disorders
Allergic reaction	6/47 (12.8%)		2/44 (4.5%)
Metabolism and nutrition disorders
ALT	5/47 (10.6%)		3/44 (6.8%)
Hyperglycemia	6/47 (12.8%)		3/44 (6.8%)
Hyperuricemia	2/47 (4.3%)		3/44 (6.8%)
Hypokalemia	5/47 (10.6%)		1/44 (2.3%)
Hypomagnesemia	2/47 (4.3%)		4/44 (9.1%)
Hyponatremia	8/47 (17%)		4/44 (9.1%)
Hypophosphatemia	6/47 (12.8%)		0/44 (0%)
Lipase	9/47 (19.1%)		2/44 (4.5%)
Nervous system disorders
Neuropathy: sensory	8/47 (17%)		12/44 (27.3%)
Respiratory, thoracic and mediastinal disorders
Cough	4/47 (8.5%)		0/44 (0%)
Dyspnea (shortness of breath)	3/47 (6.4%)		3/44 (6.8%)
Skin and subcutaneous tissue disorders
Alopecia	18/47 (38.3%)		16/44 (36.4%)
Hand-foot skin reaction	19/47 (40.4%)		2/44 (4.5%)
Rash/Desquamation	23/47 (48.9%)		6/44 (13.6%)

Limitations/Caveats

Due to early termination of the study, no comparison of treatments was possible. This study also provided limited opportunity to distinguish between Adverse Events associated with sorafenib and events associated with the underlying lung disease.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.